[AMBER] Missing (ATTN, need revision) and poor parameters (high penalty score) for small molecule parameters and hard time with paramfit

From: Állan Ferrari <ajrferrari.gmail.com>
Date: Sat, 22 Aug 2020 17:59:45 -0300

Dear Amber user community,

I am interested in simulating a protein - small molecule inhibitor
I optimized the small molecule geometry with Gaussian and derived RESP
Also, with parmchk2 I derived frcmod files containing small molecule
parameters to prepare the system for simulation using both parm10 and gaff.
However, there are still some missing parameters or parameters with high
penalty score totalizing 12 parameters among one bond, couple angles and

I have tried for days to use paramfit following this tutorial (
http://ambermd.org/tutorials/advanced/tutorial23/ ) but with no success.
In my first attempt, I have tried to generate a large number of conformers
(> 1000) with random values for the angles and dihedrals I am interested in
parametrizing. Then, I runned Gaussian to evaluate its energy (constrained,
single point energy calculation). When I tried to derive K (the
difference between Amber energy and quantum energy, in Hartree) using
paramfit the fit was horrible (R2 was negative!).

In a second attempt, I tried to generate only the r_eq and bond force
constant for one bond. I generaeed 50 conformers with random distances
between the two atoms of interest (0.5 to 3.5 A), runned gaussian single
energy point calculation for each and when it came to derive K again an
horrible fit (r2 < 0.05)! I tried to continue the tutorial regardless of
the poor fit but it didn't work, as expected. It complained I had
insufficient bond information in sample structures. Definitely not the case.

Finally, I was hoping that I could derive manually the parameters, once I
have the energies as a function of the distance between the atoms.
I fit k*(r-r0) function to the derived (E, r) data points. The k, however,
is equal to 4.5 while the k for bonds already found from parm10 and gaff
files are in the 200-600 value range.

1) Is this last attempt a valid approach, that is, vary the degree of
freedom I am interested in parametrize and then manually fit to obtain the
missing parameters?
2) Is there a multiplying factor for this parameter (10E-2?) that would
justify the difference I am observing (4.5 to 200-600)?

If (1) is not an option, I would really appreciate a better
tutorial/documentation for paramfit or other source for small molecule
amber parametrization...

Kind regards,
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Received on Sat Aug 22 2020 - 14:30:03 PDT
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